At the neuromuscular synapse are localized specialized structural elements that have an important role in the function of the synapse; the acetylcholine receptors for the transmitter are highly concentrated in the myofiber membrane at the synaptic site. During the development of myofibers this subsynaptic specialization arises as a consequence of interaction between nerve and muscle. Acetylcholine receptors in regenerated adult muscle accumulate at the original synaptic site in the absence of the nerve. Thus, structures remain at the synaptic site after removal of the nerve and muscle that can direct the differentiation of regenerating muscle. There is considerable evidence that the synaptic portion of the muscle fiber basal lamina directs the formation of presynaptic and postsynaptic specializations in regenerated nerve and muscle. These studies focus attention on the basal lamina as an important structure in the process of intercellular communication at regenerating neuromuscular synapses. Work in my laboratory will focus on structural and functional studies of basal lamina. The objectives are to determine: (1) how the synaptic basal lamina organizes acetylcholine receptors in regenerating muscle, (2) whether the basal lamina has a role in the differentiation of developing neuromuscular synapses, (3) whether components of the synaptic or Schwann cell basal lamina are more generally distributed in the nervous system, (4) whether the Schwann cell basal lamina has a role in nerve regeneration, and (5) what molecules the synaptic and Schwann cell basal lamina contain and how the synthesis and assembly of these molecules is regulated. For these studies a variety of surgical, light and electron microscopical, immunological, electrophysical and biochemical techniques will be used.